The ability of botulinum A toxin to denervate and relax a spastic external urethral sphincter was evaluated in a double-blind study involving five men with high spinal cord injuries and detrusor-sphincter dyssynergia. The sphincter was injected with either a low dose of botulinum A toxin or normal saline once per week for three weeks. Electromyography of the external urethral sphincter indicated denervation in the three patients who received toxin injections. The urethral pressure profile decreased an average of 25cm of water, postvoiding residual volume of urine decreased an average of 125cc, and bladder pressure during voiding decreased to an average of 30cm of water. Bulbosphincteric reflexes were more difficult to obtain, and they showed a decreased amplitude with normal latency. In the two patients who received normal saline injections, parameters were unchanged from baseline values until subsequent injection with botulinum A toxin once per week for three weeks when their responses were similar to those of the other three patients. Mild generalized weakness lasting two to three weeks was noted by three patients after initial toxin injections. The duration of the toxin's effect averaged two months. The results suggest that botulinum A toxin, an inhibitor of acetylcholine release at the neuromuscular junction, may be useful in the treatment of detrusor-sphincter dyssynergia.